1. Advani RH et al. Proc ASH 2011;Abstract 443.
Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma: A Phase 2 Study Update
Advani RH et al.
Proc ASH 2011;Abstract 443.

2. Background
Systemic anaplastic large cell lymphoma (sALCL) is a CD30-positive aggressive subtype of mature T-cell lymphoma, comprising 2-5% of all NHL cases.
76-88% of patients achieve remission with front-line treatment. However, approximately half will experience disease relapse.
Brentuximab vedotin (B-vedotin), a novel anti-CD30 antibody drug conjugate, selectively induces apoptotic death of CD30+ cells.
Current Analysis Objective: Present updated results from a Phase II, multicenter study evaluating the efficacy and safety of B-vedotin in relapsed/refractory sALCL.
Advani RH et al. Proc ASH 2011;Abstract 443.

3. Study Schema B-vedotin 1.8 mg/kg q3wk, 1-16 cycles 12-wk follow-ups
Eligibility (N = 58)
Relapsed or refractory systemic ALCL
Measurable disease ≥1.5 cm FDG-avid
ECOG PS 0-1
B-vedotin
1.8 mg/kg
q3wk, 1-16 cycles
12-wk follow-ups
After discontinuing treatment, 14 patients received a stem cell transplant (SCT)
(7 allogeneic, 7 autologous)
Primary Endpoint: Objective response rate (ORR) by independent review facility (IRF)
Secondary Endpoints: Complete remission rate (CR), duration of response, progression-free survival (PFS), overall survival (OS), safety and tolerability
Advani RH et al. Proc ASH 2011;Abstract 443.

4. Response Results Clinical response (n = 58) Objective response rate
86%
Complete remission rate
59%
Median duration of response
Objective response
13.2 mo
Response in patients with CR
Not reached
Advani RH et al. Proc ASH 2011;Abstract 443.

5. Survival Progression-free survival B-vedotin (n = 57) Hazard ratio*
p-value
Median PFS
14.5 mo
0.44
<0.001
PFS in patients with CR by subsequent transplant
Patients with CR
Events†
Median PFS
Median # of cycles received
No subsequent transplant (n = 20) 9
18.4 mo 13
Subsequent allogeneic SCT (n = 7) 3
16.9 mo 8
Subsequent autologous SCT (n = 7) 1
Not reached
Overall survival
(n = 58)
Median OS
Not reached
Estimated OS rate at 1 year
70%
Median observation time from first dose
14.7 mo
* Versus last prior therapy (5.9 mo); † Disease progression or death
Advani RH et al. Proc ASH 2011;Abstract 443.

6. Select Adverse Events (AEs)
AEs (all grades)
Peripheral sensory neuropathy (PN)*
45%
Fatigue
28%
Nausea
Diarrhea
19%
Neutropenia
17%
Myalgia
16%
Pyrexia
14%
Vomiting
Upper respiratory tract infection
12%
Rash
10%
* PN managed with dose delays and/or reductions to 1.2 mg/kg
Resolution/improvement in some or all PN events = 79%
Advani RH et al. Proc ASH 2011;Abstract 443.

7. Author Conclusions
Durable complete remissions were achieved with B-vedotin in patients with relapsed or refractory sALCL.
Complete remissions appear durable after completing treatment.
Adverse events, including peripheral neuropathy, were manageable.
Based on these results, a Phase I front-line trial is ongoing and a Phase III randomized trial for patients with ALCL and other CD30-positive mature T-cell neoplasms is planned.
Advani RH et al. Proc ASH 2011;Abstract 443.

8. Investigator Commentary: Phase II Update of B-Vedotin in Patients with Relapsed/Refractory sALCL
This is an update of a previous data set. Most of the patients were heavily pretreated, only a small percent had received a transplant. The fact that most of the patients could not get to transplant suggests their prognosis was not good.
Single agent treatment with B-vedotin resulted in a median duration of response of greater than a year, which is excellent. The median duration of response in patients who had a complete response was not reached. In baseball terms, for sALCL this is approaching a home run. This is amazing — it’s changed the lives of patients with this disease.
I believe that once the B-vedotin/CHOP (B-vedotin substituting for vincristine) study is completed, it’ll be a “slam dunk” and this will be standard of care for sALCL as primary therapy.
Interview with Craig Moskowitz, MD, January 11, 2012